Field of the Invention
The present invention relates generally to novel crystalline forms of cabozantinib (S)-malate, designated as form-M1, M2, M3, and M4 and novel crystalline forms of cabozantinib free base, form-M1, M2 and M3. The present invention also relates to process for the preparation of crystalline forms of cabozantinib (S)-malate, designated as form-M1, M2, M3, and M4 and novel crystalline forms of cabozantinib free base, form-M1, M2 and M3 as well as crystalline cabozantinib (S)-malate form N-1.
Background of the Invention
Cabozantinib (S)-malate, chemically known as N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide (S)-malate is structurally represented as Formula-I below. Cabozantinib is marketed under the trade name COMETRIQ® by Exelixis, Inc. COMETRIQ® is indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer.

The chemical structure of cabozantinib is disclosed in U.S. Pat. No. 7,579,473, which is hereby incorporated by reference. U.S. Pat. No. 8,877,776, which is also hereby incorporated by reference, discloses amorphous forms of cabozantinib L- and D-malate as well as the N-1 and N-2 polymorphs of crystalline cabozantinib L- and D-malate.
The present invention provides novel crystalline forms of cabozantinib (S)-malate and novel crystalline forms of cabozantinib free base.